Guidelines

Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.

Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.

Indications for transfusion

Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.

Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.

“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”

The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.

Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.

Blood products

Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).

“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.

He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.

Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.

Phenotype matching

Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.

Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.

Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.

How to transfuse

Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.

In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.

As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.

For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.

The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.

The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.

Non–transfusion dependent thalassemia

Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.

Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.

Indications for transfusion in NTDT patients include:
 

• Growth failure.
• Hematopoietic tumors.
• Pulmonary hypertension.
• Silent brain infarcts.
• Skin ulcers.
• Severe bone pain.
• Poor quality of life.
• Frequent hemolytic crises.
• Marked and enlarging spleen.
• Failure of secondary sex development.
• Cosmetic and facial changes.
• Pregnancy.

“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”

He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.

Alpha thalassemia major

For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.

Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.

A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.

“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.

He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.

These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.

Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.

[email protected]

Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.

Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.

Indications for transfusion

Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.

Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.

“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”

The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.

Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.

Blood products

Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).

“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.

He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.

Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.

Phenotype matching

Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.

Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.

Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.

How to transfuse

Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.

In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.

As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.

For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.

The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.

The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.

Non–transfusion dependent thalassemia

Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.

Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.

Indications for transfusion in NTDT patients include:
 

• Growth failure.
• Hematopoietic tumors.
• Pulmonary hypertension.
• Silent brain infarcts.
• Skin ulcers.
• Severe bone pain.
• Poor quality of life.
• Frequent hemolytic crises.
• Marked and enlarging spleen.
• Failure of secondary sex development.
• Cosmetic and facial changes.
• Pregnancy.

“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”

He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.

Alpha thalassemia major

For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.

Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.

A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.

“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.

He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.

These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.

Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.

[email protected]

Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.

Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.

Indications for transfusion

Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.

Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.

“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”

The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.

Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.

Blood products

Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).

“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.

He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.

Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.

Phenotype matching

Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.

Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.

Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.

How to transfuse

Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.

In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.

As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.

For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.

The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.

The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.

Non–transfusion dependent thalassemia

Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.

Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.

Indications for transfusion in NTDT patients include:
 

• Growth failure.
• Hematopoietic tumors.
• Pulmonary hypertension.
• Silent brain infarcts.
• Skin ulcers.
• Severe bone pain.
• Poor quality of life.
• Frequent hemolytic crises.
• Marked and enlarging spleen.
• Failure of secondary sex development.
• Cosmetic and facial changes.
• Pregnancy.

“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”

He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.

Alpha thalassemia major

For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.

Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.

A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.

“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.

He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.

These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.

Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.

[email protected]

Two new guidelines on the treatment and prevention of migraines in children and adolescents have been released by the American Academy of Neurology and the American Headache Society.

This update to the previous guidelines released by the American Academy of Neurology in 2004 reflects the expansion in pharmacologic and nonpharmacologic approaches during the last 15 years, Andrew D. Hershey, MD, PhD, director of the division of neurology at Cincinnati Children’s Hospital and a fellow of the American Academy of Neurology, said in an interview.

“There has also been an increase in the number of randomized controlled studies, which have allowed for a more robust statement on acute and preventive treatments to be made,” said Dr. Hershey, who is also a senior author for both guidelines.

The two reports focused on separate issues: One guideline outlined the options for treatment of acute migraine, and the second guideline summarized the available studies on the effectiveness of preventive medications for migraine in children and adolescents.

The guidelines recommend a physical examination and history to establish a specific headache diagnosis and afford a treatment that provides fast and complete pain relief. Treatment should be initiated as soon as a patient realizes an attack is occurring. Patients with signs of secondary headache should be evaluated by a neurologist or a headache specialist.

Studies support the use of ibuprofen and acetaminophen for pain relief in cases of acute migraine, but only some triptans (such as almotriptan, rizatriptan, sumatriptan/naproxen, and zolmitriptan nasal spray) are approved for use in adolescents. Specifically, sumatriptan/naproxen was shown to be effective when compared with placebo in studies with adolescents, whose headache symptoms resolved within 2 hours.

It may be necessary to try more than one triptan, the guidelines noted, because patients respond differently to medications. A failure to respond to one triptan does not necessarily mean that treatment with another triptan will be unsuccessful.

The guidelines also focused on patient and family education to improve medication safety and adherence. Lifestyle modification, avoidance of migraine triggers, creating good sleep habits, and staying hydrated can help reduce migraines. While no medications improved associated symptoms of migraines such as nausea or vomiting, triptans did show a benefit in reducing phonophobia and photophobia.

Evidence for pharmacologic prevention of migraines in children and adolescents is limited, according to the guidelines. In the 15 studies included in a literature review, there was not sufficient evidence to show preventive treatments, such as divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, and flunarizine, were more effective than placebo at reducing the frequency of headaches. There was some evidence to show propranolol in children and topiramate and cinnarizine in children and adolescents can reduce headache frequency. Children and adolescents who received cognitive-behavioral therapy together with amitriptyline were more likely to have reduced frequency of headaches than were those who received amitriptyline with patient education.

“The consensus conclusion was that a multidisciplinary approach that combines acute treatments, preventive treatments, and healthy habits is likely to have the best outcomes,” said Dr. Hershey.

Dr. Hershey acknowledged the many gaps between what is clinically observed and what the studies in the guidelines demonstrated.

“One of the biggest questions is how to minimize the expectation response in the controlled studies,” he said. “Additionally, we are moving toward a better recognition of the mechanism by which the various treatments work in a genetic-based disease that is polygenic in nature” with up to 38 different gene polymorphisms identified to date.

The guidelines also do not address newer treatments, such as calcitonin gene–related peptide (CGRP) antibodies, CGRP antagonists, serotonin antagonists, and devices because there are as yet no studies of their effectiveness in children and adolescents.

“They have been studied in adults, so will be prone to the expectation response; but given the large number of diverse therapies, one can hope that many of the gaps can be filled,” said Dr. Hershey.

The American Academy of Neurology provided funding for development of the guidelines and reimbursed authors who served as subcommittee members for travel expenses and in-person meetings. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, grants, honorariums, consultancies, and publishing royalties for pharmaceutical companies and other organizations.

SOURCES: Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008095. Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008105.

Two new guidelines on the treatment and prevention of migraines in children and adolescents have been released by the American Academy of Neurology and the American Headache Society.

This update to the previous guidelines released by the American Academy of Neurology in 2004 reflects the expansion in pharmacologic and nonpharmacologic approaches during the last 15 years, Andrew D. Hershey, MD, PhD, director of the division of neurology at Cincinnati Children’s Hospital and a fellow of the American Academy of Neurology, said in an interview.

“There has also been an increase in the number of randomized controlled studies, which have allowed for a more robust statement on acute and preventive treatments to be made,” said Dr. Hershey, who is also a senior author for both guidelines.

The two reports focused on separate issues: One guideline outlined the options for treatment of acute migraine, and the second guideline summarized the available studies on the effectiveness of preventive medications for migraine in children and adolescents.

The guidelines recommend a physical examination and history to establish a specific headache diagnosis and afford a treatment that provides fast and complete pain relief. Treatment should be initiated as soon as a patient realizes an attack is occurring. Patients with signs of secondary headache should be evaluated by a neurologist or a headache specialist.

Studies support the use of ibuprofen and acetaminophen for pain relief in cases of acute migraine, but only some triptans (such as almotriptan, rizatriptan, sumatriptan/naproxen, and zolmitriptan nasal spray) are approved for use in adolescents. Specifically, sumatriptan/naproxen was shown to be effective when compared with placebo in studies with adolescents, whose headache symptoms resolved within 2 hours.

It may be necessary to try more than one triptan, the guidelines noted, because patients respond differently to medications. A failure to respond to one triptan does not necessarily mean that treatment with another triptan will be unsuccessful.

The guidelines also focused on patient and family education to improve medication safety and adherence. Lifestyle modification, avoidance of migraine triggers, creating good sleep habits, and staying hydrated can help reduce migraines. While no medications improved associated symptoms of migraines such as nausea or vomiting, triptans did show a benefit in reducing phonophobia and photophobia.

Evidence for pharmacologic prevention of migraines in children and adolescents is limited, according to the guidelines. In the 15 studies included in a literature review, there was not sufficient evidence to show preventive treatments, such as divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, and flunarizine, were more effective than placebo at reducing the frequency of headaches. There was some evidence to show propranolol in children and topiramate and cinnarizine in children and adolescents can reduce headache frequency. Children and adolescents who received cognitive-behavioral therapy together with amitriptyline were more likely to have reduced frequency of headaches than were those who received amitriptyline with patient education.

“The consensus conclusion was that a multidisciplinary approach that combines acute treatments, preventive treatments, and healthy habits is likely to have the best outcomes,” said Dr. Hershey.

Dr. Hershey acknowledged the many gaps between what is clinically observed and what the studies in the guidelines demonstrated.

“One of the biggest questions is how to minimize the expectation response in the controlled studies,” he said. “Additionally, we are moving toward a better recognition of the mechanism by which the various treatments work in a genetic-based disease that is polygenic in nature” with up to 38 different gene polymorphisms identified to date.

The guidelines also do not address newer treatments, such as calcitonin gene–related peptide (CGRP) antibodies, CGRP antagonists, serotonin antagonists, and devices because there are as yet no studies of their effectiveness in children and adolescents.

“They have been studied in adults, so will be prone to the expectation response; but given the large number of diverse therapies, one can hope that many of the gaps can be filled,” said Dr. Hershey.

The American Academy of Neurology provided funding for development of the guidelines and reimbursed authors who served as subcommittee members for travel expenses and in-person meetings. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, grants, honorariums, consultancies, and publishing royalties for pharmaceutical companies and other organizations.

SOURCES: Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008095. Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008105.

Two new guidelines on the treatment and prevention of migraines in children and adolescents have been released by the American Academy of Neurology and the American Headache Society.

This update to the previous guidelines released by the American Academy of Neurology in 2004 reflects the expansion in pharmacologic and nonpharmacologic approaches during the last 15 years, Andrew D. Hershey, MD, PhD, director of the division of neurology at Cincinnati Children’s Hospital and a fellow of the American Academy of Neurology, said in an interview.

“There has also been an increase in the number of randomized controlled studies, which have allowed for a more robust statement on acute and preventive treatments to be made,” said Dr. Hershey, who is also a senior author for both guidelines.

The two reports focused on separate issues: One guideline outlined the options for treatment of acute migraine, and the second guideline summarized the available studies on the effectiveness of preventive medications for migraine in children and adolescents.

The guidelines recommend a physical examination and history to establish a specific headache diagnosis and afford a treatment that provides fast and complete pain relief. Treatment should be initiated as soon as a patient realizes an attack is occurring. Patients with signs of secondary headache should be evaluated by a neurologist or a headache specialist.

Studies support the use of ibuprofen and acetaminophen for pain relief in cases of acute migraine, but only some triptans (such as almotriptan, rizatriptan, sumatriptan/naproxen, and zolmitriptan nasal spray) are approved for use in adolescents. Specifically, sumatriptan/naproxen was shown to be effective when compared with placebo in studies with adolescents, whose headache symptoms resolved within 2 hours.

It may be necessary to try more than one triptan, the guidelines noted, because patients respond differently to medications. A failure to respond to one triptan does not necessarily mean that treatment with another triptan will be unsuccessful.

The guidelines also focused on patient and family education to improve medication safety and adherence. Lifestyle modification, avoidance of migraine triggers, creating good sleep habits, and staying hydrated can help reduce migraines. While no medications improved associated symptoms of migraines such as nausea or vomiting, triptans did show a benefit in reducing phonophobia and photophobia.

Evidence for pharmacologic prevention of migraines in children and adolescents is limited, according to the guidelines. In the 15 studies included in a literature review, there was not sufficient evidence to show preventive treatments, such as divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, and flunarizine, were more effective than placebo at reducing the frequency of headaches. There was some evidence to show propranolol in children and topiramate and cinnarizine in children and adolescents can reduce headache frequency. Children and adolescents who received cognitive-behavioral therapy together with amitriptyline were more likely to have reduced frequency of headaches than were those who received amitriptyline with patient education.

“The consensus conclusion was that a multidisciplinary approach that combines acute treatments, preventive treatments, and healthy habits is likely to have the best outcomes,” said Dr. Hershey.

Dr. Hershey acknowledged the many gaps between what is clinically observed and what the studies in the guidelines demonstrated.

“One of the biggest questions is how to minimize the expectation response in the controlled studies,” he said. “Additionally, we are moving toward a better recognition of the mechanism by which the various treatments work in a genetic-based disease that is polygenic in nature” with up to 38 different gene polymorphisms identified to date.

The guidelines also do not address newer treatments, such as calcitonin gene–related peptide (CGRP) antibodies, CGRP antagonists, serotonin antagonists, and devices because there are as yet no studies of their effectiveness in children and adolescents.

“They have been studied in adults, so will be prone to the expectation response; but given the large number of diverse therapies, one can hope that many of the gaps can be filled,” said Dr. Hershey.

The American Academy of Neurology provided funding for development of the guidelines and reimbursed authors who served as subcommittee members for travel expenses and in-person meetings. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, grants, honorariums, consultancies, and publishing royalties for pharmaceutical companies and other organizations.

SOURCES: Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008095. Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008105.

The U.S. Preventive Services Task Force recommends for the first time that primary care clinicians screen adults aged 18 years and older for illicit drug use, according to a draft recommendation statement now available for public comment.

andrewsafonov/Thinkstock

The statement defines illicit drug use as “use of illegal drugs and the nonmedical use of prescription psychoactive medications (i.e., use for reasons, for duration, in amounts, or with frequency other than prescribed or use by persons other than the prescribed individual).”

The guidelines do not apply to individuals younger than 18 years, for whom the USPSTF found insufficient evidence to recommend routine screening, or to adults currently diagnosed or in treatment for a drug use disorder.

In the draft recommendation statement, available online, the USPSTF noted that several screening tools are available for use in primary care practices, including the BSTAD (Brief Screener for Tobacco, Alcohol, and Other Drugs) that consists of six questions. The task force noted that they have found “adequate evidence” that these screening tools can detect illicit drug use. In addition, they wrote that no studies offer evidence of benefits versus harms of these screening tools, and evidence of harms associated with screening are limited.

Screening intervals can be simplified by screening young adults whenever they seek medical services and when clinicians suspect illicit drug use, the USPSTF said.

When the draft recommendation is finalized, it will replace the 2008 recommendation, which found insufficient evidence for screening in adults, as well as in adolescents. New evidence since 2008 supports the value of screening for adults aged 18 years and older, including pregnant and postpartum women.

The draft recommendations are based on the results of two systematic evidence reviews that assessed the accuracy and harms of routine illicit drug use screening. The USPSTF’s review included 12 studies on the accuracy of 15 screening tools. Overall, the sensitivity of direct screening tools to identify “unhealthy use of ‘any drug’ (including illegal drugs and nonmedical use of prescription drugs) in the past month or year” ranged from 0.71 to 0.94, and the specificity ranged from 0.87 to 0.97.

Based on the current evidence, the USPSTF assigned drug screening for adults a grade B recommendation, defined as “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.”

For treatment, the Task Force found evidence to support strategies including pharmacotherapy with naltrexone, buprenorphine, and methadone, as well as for psychosocial interventions.

The USPSTF acknowledged that many factors may affect a clinicians’ decision of whether to implement the drug screening recommendation. “In many communities, affordable, accessible, and timely services for diagnostic assessment and treatment for patients with positive screening results are in limited supply or unaffordable. Providers should be aware of any state requirements for mandatory screening or reporting of screening results to medicolegal authorities and understand the positive and negative implications of reporting,” they wrote.

The draft recommendations also identified several research gaps including the effectiveness of screening for illicit drug use in adolescents, the optimal screening interval for all patients, the accuracy of screening tools for detecting opioids, the accuracy of screening within the same population, the benefits of naloxone as rescue therapy, and nonmedical use of other prescription drugs, as well as ways to improve access to care for those diagnosed with drug use disorders.

The draft recommendation is available for public comment until Sept. 9, 2019, at 8 p.m. EST.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

The U.S. Preventive Services Task Force recommends for the first time that primary care clinicians screen adults aged 18 years and older for illicit drug use, according to a draft recommendation statement now available for public comment.

andrewsafonov/Thinkstock

The statement defines illicit drug use as “use of illegal drugs and the nonmedical use of prescription psychoactive medications (i.e., use for reasons, for duration, in amounts, or with frequency other than prescribed or use by persons other than the prescribed individual).”

The guidelines do not apply to individuals younger than 18 years, for whom the USPSTF found insufficient evidence to recommend routine screening, or to adults currently diagnosed or in treatment for a drug use disorder.

In the draft recommendation statement, available online, the USPSTF noted that several screening tools are available for use in primary care practices, including the BSTAD (Brief Screener for Tobacco, Alcohol, and Other Drugs) that consists of six questions. The task force noted that they have found “adequate evidence” that these screening tools can detect illicit drug use. In addition, they wrote that no studies offer evidence of benefits versus harms of these screening tools, and evidence of harms associated with screening are limited.

Screening intervals can be simplified by screening young adults whenever they seek medical services and when clinicians suspect illicit drug use, the USPSTF said.

When the draft recommendation is finalized, it will replace the 2008 recommendation, which found insufficient evidence for screening in adults, as well as in adolescents. New evidence since 2008 supports the value of screening for adults aged 18 years and older, including pregnant and postpartum women.

The draft recommendations are based on the results of two systematic evidence reviews that assessed the accuracy and harms of routine illicit drug use screening. The USPSTF’s review included 12 studies on the accuracy of 15 screening tools. Overall, the sensitivity of direct screening tools to identify “unhealthy use of ‘any drug’ (including illegal drugs and nonmedical use of prescription drugs) in the past month or year” ranged from 0.71 to 0.94, and the specificity ranged from 0.87 to 0.97.

Based on the current evidence, the USPSTF assigned drug screening for adults a grade B recommendation, defined as “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.”

For treatment, the Task Force found evidence to support strategies including pharmacotherapy with naltrexone, buprenorphine, and methadone, as well as for psychosocial interventions.

The USPSTF acknowledged that many factors may affect a clinicians’ decision of whether to implement the drug screening recommendation. “In many communities, affordable, accessible, and timely services for diagnostic assessment and treatment for patients with positive screening results are in limited supply or unaffordable. Providers should be aware of any state requirements for mandatory screening or reporting of screening results to medicolegal authorities and understand the positive and negative implications of reporting,” they wrote.

The draft recommendations also identified several research gaps including the effectiveness of screening for illicit drug use in adolescents, the optimal screening interval for all patients, the accuracy of screening tools for detecting opioids, the accuracy of screening within the same population, the benefits of naloxone as rescue therapy, and nonmedical use of other prescription drugs, as well as ways to improve access to care for those diagnosed with drug use disorders.

The draft recommendation is available for public comment until Sept. 9, 2019, at 8 p.m. EST.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

The U.S. Preventive Services Task Force recommends for the first time that primary care clinicians screen adults aged 18 years and older for illicit drug use, according to a draft recommendation statement now available for public comment.

andrewsafonov/Thinkstock

The statement defines illicit drug use as “use of illegal drugs and the nonmedical use of prescription psychoactive medications (i.e., use for reasons, for duration, in amounts, or with frequency other than prescribed or use by persons other than the prescribed individual).”

The guidelines do not apply to individuals younger than 18 years, for whom the USPSTF found insufficient evidence to recommend routine screening, or to adults currently diagnosed or in treatment for a drug use disorder.

In the draft recommendation statement, available online, the USPSTF noted that several screening tools are available for use in primary care practices, including the BSTAD (Brief Screener for Tobacco, Alcohol, and Other Drugs) that consists of six questions. The task force noted that they have found “adequate evidence” that these screening tools can detect illicit drug use. In addition, they wrote that no studies offer evidence of benefits versus harms of these screening tools, and evidence of harms associated with screening are limited.

Screening intervals can be simplified by screening young adults whenever they seek medical services and when clinicians suspect illicit drug use, the USPSTF said.

When the draft recommendation is finalized, it will replace the 2008 recommendation, which found insufficient evidence for screening in adults, as well as in adolescents. New evidence since 2008 supports the value of screening for adults aged 18 years and older, including pregnant and postpartum women.

The draft recommendations are based on the results of two systematic evidence reviews that assessed the accuracy and harms of routine illicit drug use screening. The USPSTF’s review included 12 studies on the accuracy of 15 screening tools. Overall, the sensitivity of direct screening tools to identify “unhealthy use of ‘any drug’ (including illegal drugs and nonmedical use of prescription drugs) in the past month or year” ranged from 0.71 to 0.94, and the specificity ranged from 0.87 to 0.97.

Based on the current evidence, the USPSTF assigned drug screening for adults a grade B recommendation, defined as “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.”

For treatment, the Task Force found evidence to support strategies including pharmacotherapy with naltrexone, buprenorphine, and methadone, as well as for psychosocial interventions.

The USPSTF acknowledged that many factors may affect a clinicians’ decision of whether to implement the drug screening recommendation. “In many communities, affordable, accessible, and timely services for diagnostic assessment and treatment for patients with positive screening results are in limited supply or unaffordable. Providers should be aware of any state requirements for mandatory screening or reporting of screening results to medicolegal authorities and understand the positive and negative implications of reporting,” they wrote.

The draft recommendations also identified several research gaps including the effectiveness of screening for illicit drug use in adolescents, the optimal screening interval for all patients, the accuracy of screening tools for detecting opioids, the accuracy of screening within the same population, the benefits of naloxone as rescue therapy, and nonmedical use of other prescription drugs, as well as ways to improve access to care for those diagnosed with drug use disorders.

The draft recommendation is available for public comment until Sept. 9, 2019, at 8 p.m. EST.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.

The U.S. Preventive Services Task Force has issued a recommendation statement reaffirming its 2004 guideline, which recommended against screening for pancreatic cancer in asymptomatic adults, according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and associates.

Pancreatic cancer is uncommon, with an age-adjusted annual incidence of 12.9 cases per 100,000 person-years; however, pancreatic cancer is the third most common cause of cancer death because mortality is high. The mortality rate is 11.0 deaths per 100,000 person-years, and an estimated 45,750 people will die from the disease in 2019.

In 2004, the USPSTF issued a D recommendation for pancreatic cancer screening in asymptomatic adults without a family history of pancreatic cancer or a genetic disorder that increases the risk of cancer. For the 2019 update, the task force conducted a systematic review of 13 studies that assessed the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treating screen-detected or asymptomatic pancreatic cancer.

According to the USPSTF, the studies included in the review found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves morbidity or mortality, found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small, and found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate.

Because no new evidence was found supporting pancreatic cancer screening in asymptomatic adults, “the USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms,” the task force members noted.

The task force authors reported no disclosures related to the recommendation statement.

SOURCE: Owens DK et al. JAMA. 2019 Aug 6. doi: 10.1001/jama.2019.10232.

The U.S. Preventive Services Task Force has issued a recommendation statement reaffirming its 2004 guideline, which recommended against screening for pancreatic cancer in asymptomatic adults, according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and associates.

Pancreatic cancer is uncommon, with an age-adjusted annual incidence of 12.9 cases per 100,000 person-years; however, pancreatic cancer is the third most common cause of cancer death because mortality is high. The mortality rate is 11.0 deaths per 100,000 person-years, and an estimated 45,750 people will die from the disease in 2019.

In 2004, the USPSTF issued a D recommendation for pancreatic cancer screening in asymptomatic adults without a family history of pancreatic cancer or a genetic disorder that increases the risk of cancer. For the 2019 update, the task force conducted a systematic review of 13 studies that assessed the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treating screen-detected or asymptomatic pancreatic cancer.

According to the USPSTF, the studies included in the review found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves morbidity or mortality, found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small, and found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate.

Because no new evidence was found supporting pancreatic cancer screening in asymptomatic adults, “the USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms,” the task force members noted.

The task force authors reported no disclosures related to the recommendation statement.

SOURCE: Owens DK et al. JAMA. 2019 Aug 6. doi: 10.1001/jama.2019.10232.

The U.S. Preventive Services Task Force has issued a recommendation statement reaffirming its 2004 guideline, which recommended against screening for pancreatic cancer in asymptomatic adults, according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and associates.

Pancreatic cancer is uncommon, with an age-adjusted annual incidence of 12.9 cases per 100,000 person-years; however, pancreatic cancer is the third most common cause of cancer death because mortality is high. The mortality rate is 11.0 deaths per 100,000 person-years, and an estimated 45,750 people will die from the disease in 2019.

In 2004, the USPSTF issued a D recommendation for pancreatic cancer screening in asymptomatic adults without a family history of pancreatic cancer or a genetic disorder that increases the risk of cancer. For the 2019 update, the task force conducted a systematic review of 13 studies that assessed the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treating screen-detected or asymptomatic pancreatic cancer.

According to the USPSTF, the studies included in the review found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves morbidity or mortality, found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small, and found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate.

Because no new evidence was found supporting pancreatic cancer screening in asymptomatic adults, “the USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms,” the task force members noted.

The task force authors reported no disclosures related to the recommendation statement.

SOURCE: Owens DK et al. JAMA. 2019 Aug 6. doi: 10.1001/jama.2019.10232.

A new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in children has been released by the Canadian Association of Gastroenterology (CAG).

The new guideline provides evidence-based recommendations regarding optimal medical treatment strategies for achieving clinical remission based on a multi-item assessment of disease activity in pediatric patients with luminal CD. The guideline does not address surgical management, diagnosis, psychosocial therapies, preventative health considerations, or growth monitoring.

“The implications of inadequately treated CD are of particular importance in children because of the potentially serious and irreversible consequences,” wrote David R. Mack, MD, of the University of Ottawa and associates. Dr. Mack is the lead author of the pediatric practice guideline copublished in Gastroenterology and the Journal of the Canadian Association of Gastroenterology.

The consensus group reached its recommendations based on a systematic review of the literature for studies related to the medical treatment of pediatric CD. The majority of studies were randomized trials conducted in adults with CD.

“Evidence of efficacy of specific treatments in achieving mucosal healing is limited; therefore, “complete” or “deep” remission (clinical remission plus mucosal healing) was not the chosen primary outcome,” the guideline authors wrote.

The panel recommended that corticosteroids can be used as induction therapy in children with moderate to severe disease. Moreover, budesonide may be an appropriate alternative for induction therapy in patients with mild to moderate CD.

In contrast, the group recommended against the use of corticosteroids as maintenance therapy, largely because of adverse events reported with long-term use.

At diagnosis or initial stages of severe disease, as well as in patients who have failed with immunosuppressant and corticosteroid induction strategies, enteral nutrition should be used exclusively for induction therapy. In addition, anti–tumor necrosis factor biologics are an appropriate option for induction and maintenance therapy in these patients, according to the guideline.

“The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy,” they wrote.

With respect to cannabis-based products, the panel made a strong recommendation against the use of these agents in all pediatric patients.

In terms of assessment, the team recommended that patients in clinical remission receiving methotrexate or a thiopurine agent as maintenance therapy should be evaluated for mucosal healing within 1 year of therapy initiation.

No consensus was reached on the adjuvant use of immunosuppressants during initiation therapy with a biologic drug, but the consensus panel recommended against the use of thiopurine combinations in male patients. Furthermore, no consensus was reached on the role of vedolizumab or antibiotics for induction or maintenance therapy, methotrexate for induction therapy, and the function of aminosalicylates in patients with mild CD.

The panel highlighted the importance of incorporating patient perspectives into treatment decision making.

“It is hoped that the available information will enhance the discussion between the clinician and the patient and enable the patient to make an evidence-based informed decision.”

The expert consensus was made up of 15 voting members that consisted of pediatric gastroenterologists throughout the United States and Canada, with expertise in several domains, including clinical epidemiology, nutrition, health services research, and patient engagement.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) criteria. The quality of evidence for each consensus statement was denoted as either high, moderate, low, or very low, based on the criteria.

The consensus statements were finalized at an in-person meeting conducted in Toronto in October 2017.

The guideline was supported through grant funding provided by AbbVie and Takeda. The authors reported financial affiliations with AbbVie and Takeda, as well as Janssen, Nestle Health Sciences, Shire, and several others.

SOURCE: Mack DR et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.022.

A new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in children has been released by the Canadian Association of Gastroenterology (CAG).

The new guideline provides evidence-based recommendations regarding optimal medical treatment strategies for achieving clinical remission based on a multi-item assessment of disease activity in pediatric patients with luminal CD. The guideline does not address surgical management, diagnosis, psychosocial therapies, preventative health considerations, or growth monitoring.

“The implications of inadequately treated CD are of particular importance in children because of the potentially serious and irreversible consequences,” wrote David R. Mack, MD, of the University of Ottawa and associates. Dr. Mack is the lead author of the pediatric practice guideline copublished in Gastroenterology and the Journal of the Canadian Association of Gastroenterology.

The consensus group reached its recommendations based on a systematic review of the literature for studies related to the medical treatment of pediatric CD. The majority of studies were randomized trials conducted in adults with CD.

“Evidence of efficacy of specific treatments in achieving mucosal healing is limited; therefore, “complete” or “deep” remission (clinical remission plus mucosal healing) was not the chosen primary outcome,” the guideline authors wrote.

The panel recommended that corticosteroids can be used as induction therapy in children with moderate to severe disease. Moreover, budesonide may be an appropriate alternative for induction therapy in patients with mild to moderate CD.

In contrast, the group recommended against the use of corticosteroids as maintenance therapy, largely because of adverse events reported with long-term use.

At diagnosis or initial stages of severe disease, as well as in patients who have failed with immunosuppressant and corticosteroid induction strategies, enteral nutrition should be used exclusively for induction therapy. In addition, anti–tumor necrosis factor biologics are an appropriate option for induction and maintenance therapy in these patients, according to the guideline.

“The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy,” they wrote.

With respect to cannabis-based products, the panel made a strong recommendation against the use of these agents in all pediatric patients.

In terms of assessment, the team recommended that patients in clinical remission receiving methotrexate or a thiopurine agent as maintenance therapy should be evaluated for mucosal healing within 1 year of therapy initiation.

No consensus was reached on the adjuvant use of immunosuppressants during initiation therapy with a biologic drug, but the consensus panel recommended against the use of thiopurine combinations in male patients. Furthermore, no consensus was reached on the role of vedolizumab or antibiotics for induction or maintenance therapy, methotrexate for induction therapy, and the function of aminosalicylates in patients with mild CD.

The panel highlighted the importance of incorporating patient perspectives into treatment decision making.

“It is hoped that the available information will enhance the discussion between the clinician and the patient and enable the patient to make an evidence-based informed decision.”

The expert consensus was made up of 15 voting members that consisted of pediatric gastroenterologists throughout the United States and Canada, with expertise in several domains, including clinical epidemiology, nutrition, health services research, and patient engagement.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) criteria. The quality of evidence for each consensus statement was denoted as either high, moderate, low, or very low, based on the criteria.

The consensus statements were finalized at an in-person meeting conducted in Toronto in October 2017.

The guideline was supported through grant funding provided by AbbVie and Takeda. The authors reported financial affiliations with AbbVie and Takeda, as well as Janssen, Nestle Health Sciences, Shire, and several others.

SOURCE: Mack DR et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.022.

A new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in children has been released by the Canadian Association of Gastroenterology (CAG).

The new guideline provides evidence-based recommendations regarding optimal medical treatment strategies for achieving clinical remission based on a multi-item assessment of disease activity in pediatric patients with luminal CD. The guideline does not address surgical management, diagnosis, psychosocial therapies, preventative health considerations, or growth monitoring.

“The implications of inadequately treated CD are of particular importance in children because of the potentially serious and irreversible consequences,” wrote David R. Mack, MD, of the University of Ottawa and associates. Dr. Mack is the lead author of the pediatric practice guideline copublished in Gastroenterology and the Journal of the Canadian Association of Gastroenterology.

The consensus group reached its recommendations based on a systematic review of the literature for studies related to the medical treatment of pediatric CD. The majority of studies were randomized trials conducted in adults with CD.

“Evidence of efficacy of specific treatments in achieving mucosal healing is limited; therefore, “complete” or “deep” remission (clinical remission plus mucosal healing) was not the chosen primary outcome,” the guideline authors wrote.

The panel recommended that corticosteroids can be used as induction therapy in children with moderate to severe disease. Moreover, budesonide may be an appropriate alternative for induction therapy in patients with mild to moderate CD.

In contrast, the group recommended against the use of corticosteroids as maintenance therapy, largely because of adverse events reported with long-term use.

At diagnosis or initial stages of severe disease, as well as in patients who have failed with immunosuppressant and corticosteroid induction strategies, enteral nutrition should be used exclusively for induction therapy. In addition, anti–tumor necrosis factor biologics are an appropriate option for induction and maintenance therapy in these patients, according to the guideline.

“The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy,” they wrote.

With respect to cannabis-based products, the panel made a strong recommendation against the use of these agents in all pediatric patients.

In terms of assessment, the team recommended that patients in clinical remission receiving methotrexate or a thiopurine agent as maintenance therapy should be evaluated for mucosal healing within 1 year of therapy initiation.

No consensus was reached on the adjuvant use of immunosuppressants during initiation therapy with a biologic drug, but the consensus panel recommended against the use of thiopurine combinations in male patients. Furthermore, no consensus was reached on the role of vedolizumab or antibiotics for induction or maintenance therapy, methotrexate for induction therapy, and the function of aminosalicylates in patients with mild CD.

The panel highlighted the importance of incorporating patient perspectives into treatment decision making.

“It is hoped that the available information will enhance the discussion between the clinician and the patient and enable the patient to make an evidence-based informed decision.”

The expert consensus was made up of 15 voting members that consisted of pediatric gastroenterologists throughout the United States and Canada, with expertise in several domains, including clinical epidemiology, nutrition, health services research, and patient engagement.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) criteria. The quality of evidence for each consensus statement was denoted as either high, moderate, low, or very low, based on the criteria.

The consensus statements were finalized at an in-person meeting conducted in Toronto in October 2017.

The guideline was supported through grant funding provided by AbbVie and Takeda. The authors reported financial affiliations with AbbVie and Takeda, as well as Janssen, Nestle Health Sciences, Shire, and several others.

SOURCE: Mack DR et al. Gastroenterology. 2019. doi: 10.1053/j.gastro.2019.03.022.

The Canadian Association of Gastroenterology has released a new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in adults.

“In the last decade, treatment paradigms have changed, recognizing that certain clinical parameters carry an increased risk of progressive and disabling disease,” wrote Remo Panaccione, MD, of the University of Calgary (Canada) and collaborators. Dr. Panaccione is the lead author of this practice guideline copublished in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

The expert consensus panel consisted of 20 voting members, including both academic and community gastroenterologists, in addition to a specialist nurse practitioner. Other nonvoting members included two GRADE experts, lay observers, and a patient representative.

The panel systematically reviewed the body of literature for studies related to the management of CD in adults. After applying the search criteria, the team found that the majority of evidence was extracted from systematic reviews and meta-analyses of randomized trials.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology. The quality of evidence for each consensus statement was classified as either high, moderate, low, or very low, based on the methodology’s criteria.

The consensus statements were finalized at a face-to-face meeting in Toronto held in September 2016. Prior to completion, a web-based system was used to allow for anonymous voting on level of agreement for each consensus statement.

The new guideline provides evidence-based recommendations about optimal treatment approaches for patients with mild to severe active luminal CD in an ambulatory setting, with particular focus on six major drug classes, including corticosteroids, biologic therapies, immunosuppressants, 5-aminosalicylate, antibiotics, and other therapies.

The consensus group recommended against the use of 5-aminosalicylate or antibiotics as induction or maintenance treatment strategies. Alternatively, they suggested that corticosteroids, including budesonide, could be used as induction therapy, but not as maintenance therapy.

“Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD,” they wrote.

With respect to immunosuppressive therapy, thiopurine agents could be an appropriate option for maintenance therapy in certain low-risk patients, but were not recommended as induction therapy, according to the guideline.

In patients who fail with conventional induction therapies, Dr. Panaccione and colleagues recommended that biological treatments, including ustekinumab, vedolizumab, and anti–tumor necrosis factor agents, could be used. No consensus was reached on the concomitant use of immunosuppressants and biologics.

In recent years, an increasing amount of evidence has emphasized the importance of mucosal healing as a key goal of therapy. In particular, the use of some therapies can result in mucosal healing and symptomatic improvement in certain patients with luminal CD.

In addition, the authors explained that mucosal healing has been linked to better clinical outcomes over the short and long term. As a result, the recommendations in the guideline target complete remission, defined as both endoscopic and symptomatic remission.

“The outcome assessed in most randomized controlled trials (RCTs) has been either symptomatic remission or symptomatic response, with only more contemporary clinical trials including endoscopic outcomes,” the guideline authors wrote.

For this reason, the GRADE criteria–based quality of evidence for some of the consensus statements had to be lowered, they noted.

The panel acknowledged the importance of incorporating patient perspectives into treatment decision making; however, they reported that many gaps in clinical practice still remain.

“In many instances, factors that influence patient decisions relating to therapy choice and goals of therapy are not the same as those of the treating clinician,” they wrote. “[Current] surveys indicate a discrepancy between patient and physician treatment goals.”

In response, the guideline authors highlighted the importance of improved patient-physician collaboration and patient education.

The guideline was supported through grant funding provided by AbbVie, Janssen, Pfizer, and Takeda. The authors reported financial affiliations with AbbVie, Amgen, Baxter, Janssen, Shire, Takeda, and several others.
 

SOURCE: Panaccione R et al. Clin Gastroenterol Hepatol. 2019 Mar 7. doi: 10.1016/j.cgh.2019.02.043.

The Canadian Association of Gastroenterology has released a new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in adults.

“In the last decade, treatment paradigms have changed, recognizing that certain clinical parameters carry an increased risk of progressive and disabling disease,” wrote Remo Panaccione, MD, of the University of Calgary (Canada) and collaborators. Dr. Panaccione is the lead author of this practice guideline copublished in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

The expert consensus panel consisted of 20 voting members, including both academic and community gastroenterologists, in addition to a specialist nurse practitioner. Other nonvoting members included two GRADE experts, lay observers, and a patient representative.

The panel systematically reviewed the body of literature for studies related to the management of CD in adults. After applying the search criteria, the team found that the majority of evidence was extracted from systematic reviews and meta-analyses of randomized trials.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology. The quality of evidence for each consensus statement was classified as either high, moderate, low, or very low, based on the methodology’s criteria.

The consensus statements were finalized at a face-to-face meeting in Toronto held in September 2016. Prior to completion, a web-based system was used to allow for anonymous voting on level of agreement for each consensus statement.

The new guideline provides evidence-based recommendations about optimal treatment approaches for patients with mild to severe active luminal CD in an ambulatory setting, with particular focus on six major drug classes, including corticosteroids, biologic therapies, immunosuppressants, 5-aminosalicylate, antibiotics, and other therapies.

The consensus group recommended against the use of 5-aminosalicylate or antibiotics as induction or maintenance treatment strategies. Alternatively, they suggested that corticosteroids, including budesonide, could be used as induction therapy, but not as maintenance therapy.

“Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD,” they wrote.

With respect to immunosuppressive therapy, thiopurine agents could be an appropriate option for maintenance therapy in certain low-risk patients, but were not recommended as induction therapy, according to the guideline.

In patients who fail with conventional induction therapies, Dr. Panaccione and colleagues recommended that biological treatments, including ustekinumab, vedolizumab, and anti–tumor necrosis factor agents, could be used. No consensus was reached on the concomitant use of immunosuppressants and biologics.

In recent years, an increasing amount of evidence has emphasized the importance of mucosal healing as a key goal of therapy. In particular, the use of some therapies can result in mucosal healing and symptomatic improvement in certain patients with luminal CD.

In addition, the authors explained that mucosal healing has been linked to better clinical outcomes over the short and long term. As a result, the recommendations in the guideline target complete remission, defined as both endoscopic and symptomatic remission.

“The outcome assessed in most randomized controlled trials (RCTs) has been either symptomatic remission or symptomatic response, with only more contemporary clinical trials including endoscopic outcomes,” the guideline authors wrote.

For this reason, the GRADE criteria–based quality of evidence for some of the consensus statements had to be lowered, they noted.

The panel acknowledged the importance of incorporating patient perspectives into treatment decision making; however, they reported that many gaps in clinical practice still remain.

“In many instances, factors that influence patient decisions relating to therapy choice and goals of therapy are not the same as those of the treating clinician,” they wrote. “[Current] surveys indicate a discrepancy between patient and physician treatment goals.”

In response, the guideline authors highlighted the importance of improved patient-physician collaboration and patient education.

The guideline was supported through grant funding provided by AbbVie, Janssen, Pfizer, and Takeda. The authors reported financial affiliations with AbbVie, Amgen, Baxter, Janssen, Shire, Takeda, and several others.
 

SOURCE: Panaccione R et al. Clin Gastroenterol Hepatol. 2019 Mar 7. doi: 10.1016/j.cgh.2019.02.043.

The Canadian Association of Gastroenterology has released a new clinical practice guideline for the treatment of luminal Crohn’s disease (CD) in adults.

“In the last decade, treatment paradigms have changed, recognizing that certain clinical parameters carry an increased risk of progressive and disabling disease,” wrote Remo Panaccione, MD, of the University of Calgary (Canada) and collaborators. Dr. Panaccione is the lead author of this practice guideline copublished in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

The expert consensus panel consisted of 20 voting members, including both academic and community gastroenterologists, in addition to a specialist nurse practitioner. Other nonvoting members included two GRADE experts, lay observers, and a patient representative.

The panel systematically reviewed the body of literature for studies related to the management of CD in adults. After applying the search criteria, the team found that the majority of evidence was extracted from systematic reviews and meta-analyses of randomized trials.

Quality of evidence and risk of bias was assessed using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) methodology. The quality of evidence for each consensus statement was classified as either high, moderate, low, or very low, based on the methodology’s criteria.

The consensus statements were finalized at a face-to-face meeting in Toronto held in September 2016. Prior to completion, a web-based system was used to allow for anonymous voting on level of agreement for each consensus statement.

The new guideline provides evidence-based recommendations about optimal treatment approaches for patients with mild to severe active luminal CD in an ambulatory setting, with particular focus on six major drug classes, including corticosteroids, biologic therapies, immunosuppressants, 5-aminosalicylate, antibiotics, and other therapies.

The consensus group recommended against the use of 5-aminosalicylate or antibiotics as induction or maintenance treatment strategies. Alternatively, they suggested that corticosteroids, including budesonide, could be used as induction therapy, but not as maintenance therapy.

“Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD,” they wrote.

With respect to immunosuppressive therapy, thiopurine agents could be an appropriate option for maintenance therapy in certain low-risk patients, but were not recommended as induction therapy, according to the guideline.

In patients who fail with conventional induction therapies, Dr. Panaccione and colleagues recommended that biological treatments, including ustekinumab, vedolizumab, and anti–tumor necrosis factor agents, could be used. No consensus was reached on the concomitant use of immunosuppressants and biologics.

In recent years, an increasing amount of evidence has emphasized the importance of mucosal healing as a key goal of therapy. In particular, the use of some therapies can result in mucosal healing and symptomatic improvement in certain patients with luminal CD.

In addition, the authors explained that mucosal healing has been linked to better clinical outcomes over the short and long term. As a result, the recommendations in the guideline target complete remission, defined as both endoscopic and symptomatic remission.

“The outcome assessed in most randomized controlled trials (RCTs) has been either symptomatic remission or symptomatic response, with only more contemporary clinical trials including endoscopic outcomes,” the guideline authors wrote.

For this reason, the GRADE criteria–based quality of evidence for some of the consensus statements had to be lowered, they noted.

The panel acknowledged the importance of incorporating patient perspectives into treatment decision making; however, they reported that many gaps in clinical practice still remain.

“In many instances, factors that influence patient decisions relating to therapy choice and goals of therapy are not the same as those of the treating clinician,” they wrote. “[Current] surveys indicate a discrepancy between patient and physician treatment goals.”

In response, the guideline authors highlighted the importance of improved patient-physician collaboration and patient education.

The guideline was supported through grant funding provided by AbbVie, Janssen, Pfizer, and Takeda. The authors reported financial affiliations with AbbVie, Amgen, Baxter, Janssen, Shire, Takeda, and several others.
 

SOURCE: Panaccione R et al. Clin Gastroenterol Hepatol. 2019 Mar 7. doi: 10.1016/j.cgh.2019.02.043.

Diabetes management in adults aged 65 years and older involves special considerations, because the effects of aging on metabolic regulation can exacerbate the disease and accelerate the development of common complications, according to a new guideline on diabetes care for older adults issued by the Endocrine Society.

“The prevalence of diabetes in the United States is projected to increase dramatically during the next 3 decades as the population ages, the numbers of higher-risk minority groups increase, and people with diabetes live longer because of decreasing rates of cardiovascular deaths,” wrote Derek LeRoith, MD, of Icahn School of Medicine at Mount Sinai, New York, and his writing committee colleagues. They said their goal was to provide health care providers with guidance for the management of type 1 or type 2 diabetes in older patients, with a focus on simplifying medication regimens and management strategies to avoid “unnecessary and/or harmful adverse effects.”

The guideline, published in the Journal of Clinical Endocrinology & Metabolism, is based mainly on evidence from controlled trials in two systematic reviews that specifically focused on adults aged 65 years and older. The guideline addresses six areas of consideration for this patient population:

• Role of the endocrinologist and diabetes care specialist.
• Screening for diabetes and prediabetes, and diabetes prevention.
• Assessment of older patients with diabetes.
• Treatment of hyperglycemia.
• Treating complications of diabetes.
• Special settings and populations.

Partnerships and screening

The guideline recommends that primary care providers partner with an endocrinologist or diabetes specialist in the care of patients aged 65 and older with newly diagnosed diabetes, and that the specialist take primary responsibility for diabetes care of patients with type 1 diabetes or those who need more complex intervention to achieve treatment goals.

Screening for diabetes in adults aged 65 years and older using fasting plasma glucose and/or hemoglobin A_1c should occur every 2 years, but that schedule should be adjusted based on shared decision making with the patient, the committee said. Providers are advised to assess the patient’s overall health and personal values before settling on treatment goals and strategies. The writing group also recommends periodic cognitive screening and that medication regimens be simplified as much as possible.
 

Tackling hyperglycemia

For treatment of hyperglycemia, the guideline recommends outpatient strategies to minimize hypoglycemia and periodic or continuous glucose monitoring. The strategies include lifestyle modifications as a first-line intervention for ambulatory patients, as well as nutritional assessment. A high-protein diet is recommended for older patients with frailty, but no restrictions on diet are advised for patients who cannot meet glycemic targets with lifestyle modification and who are at risk for malnutrition.

Metformin is the first-choice recommendation for patients with diabetes aged 65 and older who need medical management in addition to lifestyle modification, but it is not recommended for individuals with impaired kidney function or gastrointestinal intolerance, according to the guideline. Oral and injectable drugs and/or insulin are recommended if metformin and lifestyle changes are insufficient to meet glycemic targets, the writers noted.
 

Managing complications

Hypertension is among the diabetes-related complications that need to be managed in older adults, and the guideline recommends a target blood pressure of 140/90 mm Hg, but other targets – based on patient-provider shared decision making – may be considered for patients in high-risk groups.

The guideline calls for management of hyperlipidemia with statin therapy and “use of an annual lipid profile to achieve the recommended levels for reducing absolute cardiovascular disease events and all-cause mortality.” The committee does not specify low-density lipoprotein cholesterol targets because of insufficient evidence, but recommends alternative treatments, including ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors, if statin therapy is not enough to help the patients meet goals. The writers also advocate fish oil and/or fenofibrate for patients with fasting triglycerides of more than 500 mg/dL.

To manage congestive heart failure in older patients with diabetes, the guideline recommends following standard clinical practice guidelines for the condition, and cautious use of oral hypoglycemic agents, including glinides, rosiglitazone, pioglitazone, and dipeptidyl peptidase–4 inhibitors. The writers noted that low-dose aspirin is recommended for patients with diabetes with a history of atherosclerotic cardiovascular disease.

The committee also recommends an annual comprehensive eye exam for patients with diabetes aged 65 years and older to identify retinal disease and suggests that actions, such as physical therapy and reduced use of sedatives, be taken to minimize the risk of falls in patients with neuropathy or problems with balance and gait.

Older patients with diabetes also should be screened annually for chronic kidney disease, and the dosage of diabetes medications should be adjusted to minimize side effects in patients with kidney problems.
 

Tailoring care to setting

Finally, the guideline addresses special settings and populations, including managing diabetes in hospitals or nursing homes, or in patients who are transitioning to homes or long-term care facilities. Recommendations in this category include simplifying medications for older adults with terminal illness or severe comorbidities, as well as setting glycemic targets as part of a hospital discharge plan.

“The most important aspect of successful transition is effective, detailed, and thorough bidirectional communication between the discharging and receiving teams of health care providers,” the writers emphasized.

The guideline is cosponsored by the European Society of Endocrinology, the Gerontological Society of America, and the Obesity Society. The chair of the committee had no relevant financial conflicts to disclose, and at least 50% of the committee members were free of relevant conflicts of interest.

SOURCE: LeRoith D et al. J Clin Endocrinol Metab. 2019;104:1520-74.

Diabetes management in adults aged 65 years and older involves special considerations, because the effects of aging on metabolic regulation can exacerbate the disease and accelerate the development of common complications, according to a new guideline on diabetes care for older adults issued by the Endocrine Society.

“The prevalence of diabetes in the United States is projected to increase dramatically during the next 3 decades as the population ages, the numbers of higher-risk minority groups increase, and people with diabetes live longer because of decreasing rates of cardiovascular deaths,” wrote Derek LeRoith, MD, of Icahn School of Medicine at Mount Sinai, New York, and his writing committee colleagues. They said their goal was to provide health care providers with guidance for the management of type 1 or type 2 diabetes in older patients, with a focus on simplifying medication regimens and management strategies to avoid “unnecessary and/or harmful adverse effects.”

The guideline, published in the Journal of Clinical Endocrinology & Metabolism, is based mainly on evidence from controlled trials in two systematic reviews that specifically focused on adults aged 65 years and older. The guideline addresses six areas of consideration for this patient population:

• Role of the endocrinologist and diabetes care specialist.
• Screening for diabetes and prediabetes, and diabetes prevention.
• Assessment of older patients with diabetes.
• Treatment of hyperglycemia.
• Treating complications of diabetes.
• Special settings and populations.

Partnerships and screening

The guideline recommends that primary care providers partner with an endocrinologist or diabetes specialist in the care of patients aged 65 and older with newly diagnosed diabetes, and that the specialist take primary responsibility for diabetes care of patients with type 1 diabetes or those who need more complex intervention to achieve treatment goals.

Screening for diabetes in adults aged 65 years and older using fasting plasma glucose and/or hemoglobin A_1c should occur every 2 years, but that schedule should be adjusted based on shared decision making with the patient, the committee said. Providers are advised to assess the patient’s overall health and personal values before settling on treatment goals and strategies. The writing group also recommends periodic cognitive screening and that medication regimens be simplified as much as possible.
 

Tackling hyperglycemia

For treatment of hyperglycemia, the guideline recommends outpatient strategies to minimize hypoglycemia and periodic or continuous glucose monitoring. The strategies include lifestyle modifications as a first-line intervention for ambulatory patients, as well as nutritional assessment. A high-protein diet is recommended for older patients with frailty, but no restrictions on diet are advised for patients who cannot meet glycemic targets with lifestyle modification and who are at risk for malnutrition.

Metformin is the first-choice recommendation for patients with diabetes aged 65 and older who need medical management in addition to lifestyle modification, but it is not recommended for individuals with impaired kidney function or gastrointestinal intolerance, according to the guideline. Oral and injectable drugs and/or insulin are recommended if metformin and lifestyle changes are insufficient to meet glycemic targets, the writers noted.
 

Managing complications

Hypertension is among the diabetes-related complications that need to be managed in older adults, and the guideline recommends a target blood pressure of 140/90 mm Hg, but other targets – based on patient-provider shared decision making – may be considered for patients in high-risk groups.

The guideline calls for management of hyperlipidemia with statin therapy and “use of an annual lipid profile to achieve the recommended levels for reducing absolute cardiovascular disease events and all-cause mortality.” The committee does not specify low-density lipoprotein cholesterol targets because of insufficient evidence, but recommends alternative treatments, including ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors, if statin therapy is not enough to help the patients meet goals. The writers also advocate fish oil and/or fenofibrate for patients with fasting triglycerides of more than 500 mg/dL.

To manage congestive heart failure in older patients with diabetes, the guideline recommends following standard clinical practice guidelines for the condition, and cautious use of oral hypoglycemic agents, including glinides, rosiglitazone, pioglitazone, and dipeptidyl peptidase–4 inhibitors. The writers noted that low-dose aspirin is recommended for patients with diabetes with a history of atherosclerotic cardiovascular disease.

The committee also recommends an annual comprehensive eye exam for patients with diabetes aged 65 years and older to identify retinal disease and suggests that actions, such as physical therapy and reduced use of sedatives, be taken to minimize the risk of falls in patients with neuropathy or problems with balance and gait.

Older patients with diabetes also should be screened annually for chronic kidney disease, and the dosage of diabetes medications should be adjusted to minimize side effects in patients with kidney problems.
 

Tailoring care to setting

Finally, the guideline addresses special settings and populations, including managing diabetes in hospitals or nursing homes, or in patients who are transitioning to homes or long-term care facilities. Recommendations in this category include simplifying medications for older adults with terminal illness or severe comorbidities, as well as setting glycemic targets as part of a hospital discharge plan.

“The most important aspect of successful transition is effective, detailed, and thorough bidirectional communication between the discharging and receiving teams of health care providers,” the writers emphasized.

The guideline is cosponsored by the European Society of Endocrinology, the Gerontological Society of America, and the Obesity Society. The chair of the committee had no relevant financial conflicts to disclose, and at least 50% of the committee members were free of relevant conflicts of interest.

SOURCE: LeRoith D et al. J Clin Endocrinol Metab. 2019;104:1520-74.

Diabetes management in adults aged 65 years and older involves special considerations, because the effects of aging on metabolic regulation can exacerbate the disease and accelerate the development of common complications, according to a new guideline on diabetes care for older adults issued by the Endocrine Society.

“The prevalence of diabetes in the United States is projected to increase dramatically during the next 3 decades as the population ages, the numbers of higher-risk minority groups increase, and people with diabetes live longer because of decreasing rates of cardiovascular deaths,” wrote Derek LeRoith, MD, of Icahn School of Medicine at Mount Sinai, New York, and his writing committee colleagues. They said their goal was to provide health care providers with guidance for the management of type 1 or type 2 diabetes in older patients, with a focus on simplifying medication regimens and management strategies to avoid “unnecessary and/or harmful adverse effects.”

The guideline, published in the Journal of Clinical Endocrinology & Metabolism, is based mainly on evidence from controlled trials in two systematic reviews that specifically focused on adults aged 65 years and older. The guideline addresses six areas of consideration for this patient population:

• Role of the endocrinologist and diabetes care specialist.
• Screening for diabetes and prediabetes, and diabetes prevention.
• Assessment of older patients with diabetes.
• Treatment of hyperglycemia.
• Treating complications of diabetes.
• Special settings and populations.

Partnerships and screening

The guideline recommends that primary care providers partner with an endocrinologist or diabetes specialist in the care of patients aged 65 and older with newly diagnosed diabetes, and that the specialist take primary responsibility for diabetes care of patients with type 1 diabetes or those who need more complex intervention to achieve treatment goals.

Screening for diabetes in adults aged 65 years and older using fasting plasma glucose and/or hemoglobin A_1c should occur every 2 years, but that schedule should be adjusted based on shared decision making with the patient, the committee said. Providers are advised to assess the patient’s overall health and personal values before settling on treatment goals and strategies. The writing group also recommends periodic cognitive screening and that medication regimens be simplified as much as possible.
 

Tackling hyperglycemia

For treatment of hyperglycemia, the guideline recommends outpatient strategies to minimize hypoglycemia and periodic or continuous glucose monitoring. The strategies include lifestyle modifications as a first-line intervention for ambulatory patients, as well as nutritional assessment. A high-protein diet is recommended for older patients with frailty, but no restrictions on diet are advised for patients who cannot meet glycemic targets with lifestyle modification and who are at risk for malnutrition.

Metformin is the first-choice recommendation for patients with diabetes aged 65 and older who need medical management in addition to lifestyle modification, but it is not recommended for individuals with impaired kidney function or gastrointestinal intolerance, according to the guideline. Oral and injectable drugs and/or insulin are recommended if metformin and lifestyle changes are insufficient to meet glycemic targets, the writers noted.
 

Managing complications

Hypertension is among the diabetes-related complications that need to be managed in older adults, and the guideline recommends a target blood pressure of 140/90 mm Hg, but other targets – based on patient-provider shared decision making – may be considered for patients in high-risk groups.

The guideline calls for management of hyperlipidemia with statin therapy and “use of an annual lipid profile to achieve the recommended levels for reducing absolute cardiovascular disease events and all-cause mortality.” The committee does not specify low-density lipoprotein cholesterol targets because of insufficient evidence, but recommends alternative treatments, including ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors, if statin therapy is not enough to help the patients meet goals. The writers also advocate fish oil and/or fenofibrate for patients with fasting triglycerides of more than 500 mg/dL.

To manage congestive heart failure in older patients with diabetes, the guideline recommends following standard clinical practice guidelines for the condition, and cautious use of oral hypoglycemic agents, including glinides, rosiglitazone, pioglitazone, and dipeptidyl peptidase–4 inhibitors. The writers noted that low-dose aspirin is recommended for patients with diabetes with a history of atherosclerotic cardiovascular disease.

The committee also recommends an annual comprehensive eye exam for patients with diabetes aged 65 years and older to identify retinal disease and suggests that actions, such as physical therapy and reduced use of sedatives, be taken to minimize the risk of falls in patients with neuropathy or problems with balance and gait.

Older patients with diabetes also should be screened annually for chronic kidney disease, and the dosage of diabetes medications should be adjusted to minimize side effects in patients with kidney problems.
 

Tailoring care to setting

Finally, the guideline addresses special settings and populations, including managing diabetes in hospitals or nursing homes, or in patients who are transitioning to homes or long-term care facilities. Recommendations in this category include simplifying medications for older adults with terminal illness or severe comorbidities, as well as setting glycemic targets as part of a hospital discharge plan.

“The most important aspect of successful transition is effective, detailed, and thorough bidirectional communication between the discharging and receiving teams of health care providers,” the writers emphasized.

The guideline is cosponsored by the European Society of Endocrinology, the Gerontological Society of America, and the Obesity Society. The chair of the committee had no relevant financial conflicts to disclose, and at least 50% of the committee members were free of relevant conflicts of interest.

SOURCE: LeRoith D et al. J Clin Endocrinol Metab. 2019;104:1520-74.

A new guideline from the American Gastroenterological Association (AGA) aims to help physicians diagnose the cause of chronic watery diarrhea, particularly to exclude diagnoses other than functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS). The guideline, published in Gastroenterology, does not apply to patients with concerning presentations like weight loss/anemia, diarrhea with signs of fat malabsorption, bloody diarrhea, cases with a family history of inflammatory bowel disease (IBD), colon cancer, or celiac disease or to those who have traveled to diarrheal disease–related regions.

To rule out IBD, physicians can use either fecal calprotectin (threshold value of 50 microg/g, sensitivity, 0.81; specificity, 0.87) or fecal lactoferrin (threshold, 4.0-7.25 mcg/g; pooled sensitivity for IBD, 0.79; specificity, 0.93). Neither erythrocyte sedimentation rate (ESR) nor C-reactive protein (CRP) should be used to diagnose IBD because tests have shown low pooled sensitivity and specificity. CRP might be useful in settings in which fecal lactoferrin or calprotectin tests are not available or covered by insurance.

Patients should be tested for giardia infection, using the antigen test or PCR, because this pathogen is common in the United States and easily treated.

Patients who have not recently traveled to or from high-risk areas should not be tested for ova and parasites because this is unlikely to identify a culprit. There are other guidelines for treating patients who have traveled to high-risk countries.

Celiac disease should be tested for using immunoglobulin-A tissue transglutaminase (IgA tTG) and a second test (IgG tTG and IgG or IgA deamidated gliadin peptide, or DGP) in case the patient has IgA deficiency that could lead to a false negative on the primary test. Thresholds of 7-15 AU/mL in IgA tTG typically provide sensitivity and specificity greater than 90%. A quantitative IgA level found to be normal confirms the IgA tTG test. In abnormal findings, either IgG tTG or a test for IgG DGP can be used. If no information on IgA levels is available, IgG tTG or IgG DGP can be combined with IgA tTG. Positive celiac disease tests should be confirmed by duodenal biopsy.

Bile acid diarrhea should be tested for in the United States by measuring total bile acids in a 48-hour stool collection to document increased fecal bile acids, or serum fibroblast growth factor 19, to identify defective feedback of bile acid synthesis. The Selenium HomotauroCholic Acid Test (SeHCAT) has moderate diagnostic efficiency, but it is not available in North America. A measurement of serum levels of 7alpha-hydroxy-4-cholesten-3-one (C4), which measures bile acid synthesis, is not yet available.

No recommendation was made for using available serologic tests for the diagnosis of IBS because existing evidence suggests they lack the diagnostic accuracy needed for routine use.

The guideline development was funded by AGA and had no outside funding.

SOURCE: Smalley W et al. Gastroenterology. 2019 Jul 11. doi: 10.1053/j.gastro.2019.07.004.

A new guideline from the American Gastroenterological Association (AGA) aims to help physicians diagnose the cause of chronic watery diarrhea, particularly to exclude diagnoses other than functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS). The guideline, published in Gastroenterology, does not apply to patients with concerning presentations like weight loss/anemia, diarrhea with signs of fat malabsorption, bloody diarrhea, cases with a family history of inflammatory bowel disease (IBD), colon cancer, or celiac disease or to those who have traveled to diarrheal disease–related regions.

To rule out IBD, physicians can use either fecal calprotectin (threshold value of 50 microg/g, sensitivity, 0.81; specificity, 0.87) or fecal lactoferrin (threshold, 4.0-7.25 mcg/g; pooled sensitivity for IBD, 0.79; specificity, 0.93). Neither erythrocyte sedimentation rate (ESR) nor C-reactive protein (CRP) should be used to diagnose IBD because tests have shown low pooled sensitivity and specificity. CRP might be useful in settings in which fecal lactoferrin or calprotectin tests are not available or covered by insurance.

Patients should be tested for giardia infection, using the antigen test or PCR, because this pathogen is common in the United States and easily treated.

Patients who have not recently traveled to or from high-risk areas should not be tested for ova and parasites because this is unlikely to identify a culprit. There are other guidelines for treating patients who have traveled to high-risk countries.

Celiac disease should be tested for using immunoglobulin-A tissue transglutaminase (IgA tTG) and a second test (IgG tTG and IgG or IgA deamidated gliadin peptide, or DGP) in case the patient has IgA deficiency that could lead to a false negative on the primary test. Thresholds of 7-15 AU/mL in IgA tTG typically provide sensitivity and specificity greater than 90%. A quantitative IgA level found to be normal confirms the IgA tTG test. In abnormal findings, either IgG tTG or a test for IgG DGP can be used. If no information on IgA levels is available, IgG tTG or IgG DGP can be combined with IgA tTG. Positive celiac disease tests should be confirmed by duodenal biopsy.

Bile acid diarrhea should be tested for in the United States by measuring total bile acids in a 48-hour stool collection to document increased fecal bile acids, or serum fibroblast growth factor 19, to identify defective feedback of bile acid synthesis. The Selenium HomotauroCholic Acid Test (SeHCAT) has moderate diagnostic efficiency, but it is not available in North America. A measurement of serum levels of 7alpha-hydroxy-4-cholesten-3-one (C4), which measures bile acid synthesis, is not yet available.

No recommendation was made for using available serologic tests for the diagnosis of IBS because existing evidence suggests they lack the diagnostic accuracy needed for routine use.

The guideline development was funded by AGA and had no outside funding.

SOURCE: Smalley W et al. Gastroenterology. 2019 Jul 11. doi: 10.1053/j.gastro.2019.07.004.

A new guideline from the American Gastroenterological Association (AGA) aims to help physicians diagnose the cause of chronic watery diarrhea, particularly to exclude diagnoses other than functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS). The guideline, published in Gastroenterology, does not apply to patients with concerning presentations like weight loss/anemia, diarrhea with signs of fat malabsorption, bloody diarrhea, cases with a family history of inflammatory bowel disease (IBD), colon cancer, or celiac disease or to those who have traveled to diarrheal disease–related regions.

To rule out IBD, physicians can use either fecal calprotectin (threshold value of 50 microg/g, sensitivity, 0.81; specificity, 0.87) or fecal lactoferrin (threshold, 4.0-7.25 mcg/g; pooled sensitivity for IBD, 0.79; specificity, 0.93). Neither erythrocyte sedimentation rate (ESR) nor C-reactive protein (CRP) should be used to diagnose IBD because tests have shown low pooled sensitivity and specificity. CRP might be useful in settings in which fecal lactoferrin or calprotectin tests are not available or covered by insurance.

Patients should be tested for giardia infection, using the antigen test or PCR, because this pathogen is common in the United States and easily treated.

Patients who have not recently traveled to or from high-risk areas should not be tested for ova and parasites because this is unlikely to identify a culprit. There are other guidelines for treating patients who have traveled to high-risk countries.

Celiac disease should be tested for using immunoglobulin-A tissue transglutaminase (IgA tTG) and a second test (IgG tTG and IgG or IgA deamidated gliadin peptide, or DGP) in case the patient has IgA deficiency that could lead to a false negative on the primary test. Thresholds of 7-15 AU/mL in IgA tTG typically provide sensitivity and specificity greater than 90%. A quantitative IgA level found to be normal confirms the IgA tTG test. In abnormal findings, either IgG tTG or a test for IgG DGP can be used. If no information on IgA levels is available, IgG tTG or IgG DGP can be combined with IgA tTG. Positive celiac disease tests should be confirmed by duodenal biopsy.

Bile acid diarrhea should be tested for in the United States by measuring total bile acids in a 48-hour stool collection to document increased fecal bile acids, or serum fibroblast growth factor 19, to identify defective feedback of bile acid synthesis. The Selenium HomotauroCholic Acid Test (SeHCAT) has moderate diagnostic efficiency, but it is not available in North America. A measurement of serum levels of 7alpha-hydroxy-4-cholesten-3-one (C4), which measures bile acid synthesis, is not yet available.

No recommendation was made for using available serologic tests for the diagnosis of IBS because existing evidence suggests they lack the diagnostic accuracy needed for routine use.

The guideline development was funded by AGA and had no outside funding.

SOURCE: Smalley W et al. Gastroenterology. 2019 Jul 11. doi: 10.1053/j.gastro.2019.07.004.

MADRID – Low-dose aspirin is recommended for the primary prevention of antiphospholipid syndrome (APS) in patients at high risk for developing the condition, according to new recommendations developed by the European League Against Rheumatism (EULAR).

Sara Freeman/MDEdge News

Indeed, the NSAID should be given at a dose of between 75 mg and 100 mg per day, in patients with a “high risk” antiphospholipid (aPL) antibody profile, including asymptomatic aPL antibody carriers, patients with systemic lupus erythematosus (SLE) without APS, and in women who are not pregnant but who have a history of obstetric APS.

The recommendations, which are the first evidence-based guidelines for adult APS to be produced by EULAR, also cover the secondary prevention of APS and how to manage individuals with recurrent episodes.

The recommendations aim to help guide practice and ultimately to improve the quality of care for patients and their outcomes following treatment, Maria G. Tektonidou, MD, PhD, said at the European Congress of Rheumatology.

The guidance is necessary as “clinical practice in APS remains highly variable,” said Dr. Tektonidou of the National and Kapodistrian University of Athens. This is perhaps because APS is a “rare disease and also because it’s a newly recognized disease – it’s only 35 years old – and knowledge about the clinical spectrum, classification, and management is continuously advancing.”

Dr. Tektonidou, who was the convener of the EULAR Task Force that wrote the recommendations, noted that they were now published in Annals of the Rheumatic Diseases and considered three main groups of patients: those with thrombotic APS, those with obstetric APS, and those with catastrophic APS (CAPS). There are three overarching principles, 12 recommendations, and 29 graded statements, she said.

The three overarching principles concerned risk stratification, general measures for managing patients who test positive for aPL antibodies, and patient education and counseling on various topics, such as treatment adherence, therapeutic drug monitoring, contraceptive use, and lifestyle interventions.

Dr. Tektonidou highlighted how risk stratification was important and that a high-risk aPL profile was defined as the presence of lupus anticoagulant (LA) on at least two occasions, measured 12 weeks apart according to International Society on Thrombosis and Haemostasis guidelines, or the presence of two or even three aPL antibodies, or persistently high aPL antibody titers. By contrast, a low-risk aPL profile was defined as the isolated presence of anticardiolipin (aCL) or anti–beta-2 glycoprotein I antibodies at low-medium titers, particularly if transiently positive.

“Risk stratification should include the determination of the high-risk aPL profile; a prior history of thrombotic or obstetric [APS]; the coexistence of other systemic autoimmune diseases, and the presence of traditional cardiovascular risk factors,” Dr. Tektonidou said.

Four of the recommendations focus on the secondary prevention of APS, giving guidance on anticoagulant treatment with definite APS, first provoked or unprovoked venous thrombosis, and how to manage recurrent venous thrombosis. There also is a recommendation for the management of patients with definite APS and a first arterial thrombosis, outlining the type and intensity of anticoagulant therapy that should be given. Another four of the recommendations focus on the management of obstetric APS, with a focus on how to manage the various types of complications seen in pregnant women. Then the final recommendation concerns CAPS, it’s prevention and first-line treatment, and how to manage refractory patients.

Sara Freeman/MDEdge News

With regards to CAPS, Ricard Cervera, MD, PhD, of the Hospital Clinic of Barcelona, this is “terrible” but “thankfully rare” form of APS that was first described in the early 1990s.

Although fewer than 1% of the APS adult population have CAPS (Arthritis Rheum. 2002;46[4]:1019-27), it’s a condition in which several thrombotic events occur simultaneously, affecting multiple systems or organs and which can be life threatening if not treated quickly.
 

New treatment guidelines for catastrophic APS

During a separate clinical science session at the conference, Dr. Cervera discussed the development of treatment guidelines for CAPS, noting that this had been one of the focus points of the McMaster RARE-Bestpractices project group in 2016. The group selected CAPS for a pilot exercise in guideline development for a rare disease and published their recommendations in 2018 (J Thromb Haemost. 2018;16:1656-64). Ten recommendations were developed, most of which were conditional, Dr. Cervera said, due to the lack of, or very low certainty, of the evidence.

The new EULAR 2019 adult APS recommendations now include CAPS and recommendation number 12 is split into two parts. The first, part A, states that prompt treatment of infections is needed in all patients positive for aPL antibodies and that anticoagulation should have minimal interruption or be used at level to help prevent the development of CAPS.

The second, part B, states that the first-line treatment of CAPS should be a triple combination therapy of glucocorticoids, heparin, and plasma exchange, or intravenous immunoglobulins, rather than single-agent treatment. Plus, it says that any triggering factor should be treated accordingly.

“Finally,” Dr. Cervera said, “in patients with refractory CAPS, B-cell depletion with rituximab or complement inhibitors, for example eculizumab, may be considered.”

The adult APS recommendations project was funded by EULAR. Dr. Tektonidou and Dr. Cervera reported having no relevant conflicts of interest.

SOURCES: Tektonidou M. Ann Rheum Dis. Jun 2019;78(Suppl 2):59-60. Abstract SP0191, doi: 0.1136/annrheumdis-2019-eular.8601; and Cervera R et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):62. Abstract SP0201. doi: 10.1136/annrheumdis-2019-eular.8444.

MADRID – Low-dose aspirin is recommended for the primary prevention of antiphospholipid syndrome (APS) in patients at high risk for developing the condition, according to new recommendations developed by the European League Against Rheumatism (EULAR).

Sara Freeman/MDEdge News

Indeed, the NSAID should be given at a dose of between 75 mg and 100 mg per day, in patients with a “high risk” antiphospholipid (aPL) antibody profile, including asymptomatic aPL antibody carriers, patients with systemic lupus erythematosus (SLE) without APS, and in women who are not pregnant but who have a history of obstetric APS.

The recommendations, which are the first evidence-based guidelines for adult APS to be produced by EULAR, also cover the secondary prevention of APS and how to manage individuals with recurrent episodes.

The recommendations aim to help guide practice and ultimately to improve the quality of care for patients and their outcomes following treatment, Maria G. Tektonidou, MD, PhD, said at the European Congress of Rheumatology.

The guidance is necessary as “clinical practice in APS remains highly variable,” said Dr. Tektonidou of the National and Kapodistrian University of Athens. This is perhaps because APS is a “rare disease and also because it’s a newly recognized disease – it’s only 35 years old – and knowledge about the clinical spectrum, classification, and management is continuously advancing.”

Dr. Tektonidou, who was the convener of the EULAR Task Force that wrote the recommendations, noted that they were now published in Annals of the Rheumatic Diseases and considered three main groups of patients: those with thrombotic APS, those with obstetric APS, and those with catastrophic APS (CAPS). There are three overarching principles, 12 recommendations, and 29 graded statements, she said.

The three overarching principles concerned risk stratification, general measures for managing patients who test positive for aPL antibodies, and patient education and counseling on various topics, such as treatment adherence, therapeutic drug monitoring, contraceptive use, and lifestyle interventions.

Dr. Tektonidou highlighted how risk stratification was important and that a high-risk aPL profile was defined as the presence of lupus anticoagulant (LA) on at least two occasions, measured 12 weeks apart according to International Society on Thrombosis and Haemostasis guidelines, or the presence of two or even three aPL antibodies, or persistently high aPL antibody titers. By contrast, a low-risk aPL profile was defined as the isolated presence of anticardiolipin (aCL) or anti–beta-2 glycoprotein I antibodies at low-medium titers, particularly if transiently positive.

“Risk stratification should include the determination of the high-risk aPL profile; a prior history of thrombotic or obstetric [APS]; the coexistence of other systemic autoimmune diseases, and the presence of traditional cardiovascular risk factors,” Dr. Tektonidou said.

Four of the recommendations focus on the secondary prevention of APS, giving guidance on anticoagulant treatment with definite APS, first provoked or unprovoked venous thrombosis, and how to manage recurrent venous thrombosis. There also is a recommendation for the management of patients with definite APS and a first arterial thrombosis, outlining the type and intensity of anticoagulant therapy that should be given. Another four of the recommendations focus on the management of obstetric APS, with a focus on how to manage the various types of complications seen in pregnant women. Then the final recommendation concerns CAPS, it’s prevention and first-line treatment, and how to manage refractory patients.

Sara Freeman/MDEdge News

With regards to CAPS, Ricard Cervera, MD, PhD, of the Hospital Clinic of Barcelona, this is “terrible” but “thankfully rare” form of APS that was first described in the early 1990s.

Although fewer than 1% of the APS adult population have CAPS (Arthritis Rheum. 2002;46[4]:1019-27), it’s a condition in which several thrombotic events occur simultaneously, affecting multiple systems or organs and which can be life threatening if not treated quickly.
 

New treatment guidelines for catastrophic APS

During a separate clinical science session at the conference, Dr. Cervera discussed the development of treatment guidelines for CAPS, noting that this had been one of the focus points of the McMaster RARE-Bestpractices project group in 2016. The group selected CAPS for a pilot exercise in guideline development for a rare disease and published their recommendations in 2018 (J Thromb Haemost. 2018;16:1656-64). Ten recommendations were developed, most of which were conditional, Dr. Cervera said, due to the lack of, or very low certainty, of the evidence.

The new EULAR 2019 adult APS recommendations now include CAPS and recommendation number 12 is split into two parts. The first, part A, states that prompt treatment of infections is needed in all patients positive for aPL antibodies and that anticoagulation should have minimal interruption or be used at level to help prevent the development of CAPS.

The second, part B, states that the first-line treatment of CAPS should be a triple combination therapy of glucocorticoids, heparin, and plasma exchange, or intravenous immunoglobulins, rather than single-agent treatment. Plus, it says that any triggering factor should be treated accordingly.

“Finally,” Dr. Cervera said, “in patients with refractory CAPS, B-cell depletion with rituximab or complement inhibitors, for example eculizumab, may be considered.”

The adult APS recommendations project was funded by EULAR. Dr. Tektonidou and Dr. Cervera reported having no relevant conflicts of interest.

SOURCES: Tektonidou M. Ann Rheum Dis. Jun 2019;78(Suppl 2):59-60. Abstract SP0191, doi: 0.1136/annrheumdis-2019-eular.8601; and Cervera R et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):62. Abstract SP0201. doi: 10.1136/annrheumdis-2019-eular.8444.

MADRID – Low-dose aspirin is recommended for the primary prevention of antiphospholipid syndrome (APS) in patients at high risk for developing the condition, according to new recommendations developed by the European League Against Rheumatism (EULAR).

Sara Freeman/MDEdge News

Indeed, the NSAID should be given at a dose of between 75 mg and 100 mg per day, in patients with a “high risk” antiphospholipid (aPL) antibody profile, including asymptomatic aPL antibody carriers, patients with systemic lupus erythematosus (SLE) without APS, and in women who are not pregnant but who have a history of obstetric APS.

The recommendations, which are the first evidence-based guidelines for adult APS to be produced by EULAR, also cover the secondary prevention of APS and how to manage individuals with recurrent episodes.

The recommendations aim to help guide practice and ultimately to improve the quality of care for patients and their outcomes following treatment, Maria G. Tektonidou, MD, PhD, said at the European Congress of Rheumatology.

The guidance is necessary as “clinical practice in APS remains highly variable,” said Dr. Tektonidou of the National and Kapodistrian University of Athens. This is perhaps because APS is a “rare disease and also because it’s a newly recognized disease – it’s only 35 years old – and knowledge about the clinical spectrum, classification, and management is continuously advancing.”

Dr. Tektonidou, who was the convener of the EULAR Task Force that wrote the recommendations, noted that they were now published in Annals of the Rheumatic Diseases and considered three main groups of patients: those with thrombotic APS, those with obstetric APS, and those with catastrophic APS (CAPS). There are three overarching principles, 12 recommendations, and 29 graded statements, she said.

The three overarching principles concerned risk stratification, general measures for managing patients who test positive for aPL antibodies, and patient education and counseling on various topics, such as treatment adherence, therapeutic drug monitoring, contraceptive use, and lifestyle interventions.

Dr. Tektonidou highlighted how risk stratification was important and that a high-risk aPL profile was defined as the presence of lupus anticoagulant (LA) on at least two occasions, measured 12 weeks apart according to International Society on Thrombosis and Haemostasis guidelines, or the presence of two or even three aPL antibodies, or persistently high aPL antibody titers. By contrast, a low-risk aPL profile was defined as the isolated presence of anticardiolipin (aCL) or anti–beta-2 glycoprotein I antibodies at low-medium titers, particularly if transiently positive.

“Risk stratification should include the determination of the high-risk aPL profile; a prior history of thrombotic or obstetric [APS]; the coexistence of other systemic autoimmune diseases, and the presence of traditional cardiovascular risk factors,” Dr. Tektonidou said.

Four of the recommendations focus on the secondary prevention of APS, giving guidance on anticoagulant treatment with definite APS, first provoked or unprovoked venous thrombosis, and how to manage recurrent venous thrombosis. There also is a recommendation for the management of patients with definite APS and a first arterial thrombosis, outlining the type and intensity of anticoagulant therapy that should be given. Another four of the recommendations focus on the management of obstetric APS, with a focus on how to manage the various types of complications seen in pregnant women. Then the final recommendation concerns CAPS, it’s prevention and first-line treatment, and how to manage refractory patients.

Sara Freeman/MDEdge News

With regards to CAPS, Ricard Cervera, MD, PhD, of the Hospital Clinic of Barcelona, this is “terrible” but “thankfully rare” form of APS that was first described in the early 1990s.

Although fewer than 1% of the APS adult population have CAPS (Arthritis Rheum. 2002;46[4]:1019-27), it’s a condition in which several thrombotic events occur simultaneously, affecting multiple systems or organs and which can be life threatening if not treated quickly.
 

New treatment guidelines for catastrophic APS

During a separate clinical science session at the conference, Dr. Cervera discussed the development of treatment guidelines for CAPS, noting that this had been one of the focus points of the McMaster RARE-Bestpractices project group in 2016. The group selected CAPS for a pilot exercise in guideline development for a rare disease and published their recommendations in 2018 (J Thromb Haemost. 2018;16:1656-64). Ten recommendations were developed, most of which were conditional, Dr. Cervera said, due to the lack of, or very low certainty, of the evidence.

The new EULAR 2019 adult APS recommendations now include CAPS and recommendation number 12 is split into two parts. The first, part A, states that prompt treatment of infections is needed in all patients positive for aPL antibodies and that anticoagulation should have minimal interruption or be used at level to help prevent the development of CAPS.

The second, part B, states that the first-line treatment of CAPS should be a triple combination therapy of glucocorticoids, heparin, and plasma exchange, or intravenous immunoglobulins, rather than single-agent treatment. Plus, it says that any triggering factor should be treated accordingly.

“Finally,” Dr. Cervera said, “in patients with refractory CAPS, B-cell depletion with rituximab or complement inhibitors, for example eculizumab, may be considered.”

The adult APS recommendations project was funded by EULAR. Dr. Tektonidou and Dr. Cervera reported having no relevant conflicts of interest.

SOURCES: Tektonidou M. Ann Rheum Dis. Jun 2019;78(Suppl 2):59-60. Abstract SP0191, doi: 0.1136/annrheumdis-2019-eular.8601; and Cervera R et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):62. Abstract SP0201. doi: 10.1136/annrheumdis-2019-eular.8444.

Newly updated guidelines can inform the selection of adult donors and cord blood units for allogeneic hematopoietic stem cell transplant.

The evidence-based guidelines suggest high-resolution human leukocyte antigen (HLA) matching and donor age are important when selecting adult donors, while HLA matching, cell dose, and banking practices should be considered when selecting cord blood units.

The guidelines were developed by the National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR) and were recently published in Blood.

Adult donors

The guidelines recommend high-resolution HLA typing for adult donors and patients. This means typing for HLA-A, -B, -C, and -DRB1, at minimum. Typing at other loci – DPB1, DQB1, DRB3/4/5, DQA1, and DPA1 – is “optional but often helpful.”

An 8/8 HLA-matched donor is considered optimal. If only 7/8-matched donors are available, select a donor with a single allele mismatched at the patient’s homozygous locus if possible, and select an HLA-C*03:03 mismatch over an HLA-C*03:04 mismatch where applicable.

For both 8/8- and 7/8-matched donors, try to avoid mismatches at DQB1 and DRB3/4/5, and select DPB1 mismatches based on the DPB1 T-cell epitope algorithm. Mismatches of allotypes targeted by donor-specific HLA antibodies (DSA), including DQA1 and DPA1, should be avoided.

The guidelines recommend pursuing multiple donors because not all potential donors will be available. Younger donors should be prioritized over older donors. Other factors – such as sex or cytomegalovirus serostatus – should not affect donor selection.

Cord blood

For cord blood donations, testing attached segment identity is mandatory, red blood cell–replete units are not recommended, and both unit cryovolume and year of cryopreservation should be taken into consideration. The guidelines note that “some expert centers” favor red blood cell–depleted units with a postcryopreservation volume of about 25 ml/bag, and units banked more recently “may be linked to optimal banking practices.”

The guidelines recommend a minimum of eight high-resolution HLA typing for cord blood units and patients. A 4/6 match (HLA-A, -B, -DRB1) is acceptable, as is a 4/8 match (HLA-A, -B, -C, and -DRB1) or greater. In the case of a double-unit transplant, there is no need to match the units to each other.

“DSA must be considered on a case-by-case basis,” according to the guidelines. The patient’s diagnosis, prior immunosuppressive therapy, planned conditioning regimen, and DSA number/titer/specificity/complement fixation should be taken into consideration. DSA-targeted units should be avoided in patients with nonmalignant conditions and used with caution in patients with hematologic malignancies.

For single–cord blood units, the total nucleated cell dose should be at least 2.5 x 10⁷/kg, and the number of CD34+ cells should be at least 1.5 x 10⁵/kg. For double-unit transplants, the total nucleated cell dose should be at least 1.5 x 10⁷/kg for each unit, and the number of CD34+ cells should be at least 1.0 x 10⁵/kg for each unit.

The guidelines note that additional research is needed to inform how to balance cell dose against HLA match. However, cell dose should often take priority over HLA match for adults and larger pediatric patients, and HLA match can take priority in children, smaller adults, or patients with common HLA typing who have multiple units with a high cell dose.

The guidelines’ authors reported relationships with MolMed, NexImmune, AbbVie, Bellicum, Incyte, Medigene, Merck, Nektar, Novartis, Servier, Miltenyi, and the U.S. government/military.

[email protected]

SOURCE: Dehn J et al. Blood. 2019 Jul 10. doi: 10.1182/blood.2019001212.

Newly updated guidelines can inform the selection of adult donors and cord blood units for allogeneic hematopoietic stem cell transplant.

The evidence-based guidelines suggest high-resolution human leukocyte antigen (HLA) matching and donor age are important when selecting adult donors, while HLA matching, cell dose, and banking practices should be considered when selecting cord blood units.

The guidelines were developed by the National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR) and were recently published in Blood.

Adult donors

The guidelines recommend high-resolution HLA typing for adult donors and patients. This means typing for HLA-A, -B, -C, and -DRB1, at minimum. Typing at other loci – DPB1, DQB1, DRB3/4/5, DQA1, and DPA1 – is “optional but often helpful.”

An 8/8 HLA-matched donor is considered optimal. If only 7/8-matched donors are available, select a donor with a single allele mismatched at the patient’s homozygous locus if possible, and select an HLA-C*03:03 mismatch over an HLA-C*03:04 mismatch where applicable.

For both 8/8- and 7/8-matched donors, try to avoid mismatches at DQB1 and DRB3/4/5, and select DPB1 mismatches based on the DPB1 T-cell epitope algorithm. Mismatches of allotypes targeted by donor-specific HLA antibodies (DSA), including DQA1 and DPA1, should be avoided.

The guidelines recommend pursuing multiple donors because not all potential donors will be available. Younger donors should be prioritized over older donors. Other factors – such as sex or cytomegalovirus serostatus – should not affect donor selection.

Cord blood

For cord blood donations, testing attached segment identity is mandatory, red blood cell–replete units are not recommended, and both unit cryovolume and year of cryopreservation should be taken into consideration. The guidelines note that “some expert centers” favor red blood cell–depleted units with a postcryopreservation volume of about 25 ml/bag, and units banked more recently “may be linked to optimal banking practices.”

The guidelines recommend a minimum of eight high-resolution HLA typing for cord blood units and patients. A 4/6 match (HLA-A, -B, -DRB1) is acceptable, as is a 4/8 match (HLA-A, -B, -C, and -DRB1) or greater. In the case of a double-unit transplant, there is no need to match the units to each other.

“DSA must be considered on a case-by-case basis,” according to the guidelines. The patient’s diagnosis, prior immunosuppressive therapy, planned conditioning regimen, and DSA number/titer/specificity/complement fixation should be taken into consideration. DSA-targeted units should be avoided in patients with nonmalignant conditions and used with caution in patients with hematologic malignancies.

For single–cord blood units, the total nucleated cell dose should be at least 2.5 x 10⁷/kg, and the number of CD34+ cells should be at least 1.5 x 10⁵/kg. For double-unit transplants, the total nucleated cell dose should be at least 1.5 x 10⁷/kg for each unit, and the number of CD34+ cells should be at least 1.0 x 10⁵/kg for each unit.

The guidelines note that additional research is needed to inform how to balance cell dose against HLA match. However, cell dose should often take priority over HLA match for adults and larger pediatric patients, and HLA match can take priority in children, smaller adults, or patients with common HLA typing who have multiple units with a high cell dose.

The guidelines’ authors reported relationships with MolMed, NexImmune, AbbVie, Bellicum, Incyte, Medigene, Merck, Nektar, Novartis, Servier, Miltenyi, and the U.S. government/military.

[email protected]

SOURCE: Dehn J et al. Blood. 2019 Jul 10. doi: 10.1182/blood.2019001212.

Newly updated guidelines can inform the selection of adult donors and cord blood units for allogeneic hematopoietic stem cell transplant.

The evidence-based guidelines suggest high-resolution human leukocyte antigen (HLA) matching and donor age are important when selecting adult donors, while HLA matching, cell dose, and banking practices should be considered when selecting cord blood units.

The guidelines were developed by the National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR) and were recently published in Blood.

Adult donors

The guidelines recommend high-resolution HLA typing for adult donors and patients. This means typing for HLA-A, -B, -C, and -DRB1, at minimum. Typing at other loci – DPB1, DQB1, DRB3/4/5, DQA1, and DPA1 – is “optional but often helpful.”

An 8/8 HLA-matched donor is considered optimal. If only 7/8-matched donors are available, select a donor with a single allele mismatched at the patient’s homozygous locus if possible, and select an HLA-C*03:03 mismatch over an HLA-C*03:04 mismatch where applicable.

For both 8/8- and 7/8-matched donors, try to avoid mismatches at DQB1 and DRB3/4/5, and select DPB1 mismatches based on the DPB1 T-cell epitope algorithm. Mismatches of allotypes targeted by donor-specific HLA antibodies (DSA), including DQA1 and DPA1, should be avoided.

The guidelines recommend pursuing multiple donors because not all potential donors will be available. Younger donors should be prioritized over older donors. Other factors – such as sex or cytomegalovirus serostatus – should not affect donor selection.

Cord blood

For cord blood donations, testing attached segment identity is mandatory, red blood cell–replete units are not recommended, and both unit cryovolume and year of cryopreservation should be taken into consideration. The guidelines note that “some expert centers” favor red blood cell–depleted units with a postcryopreservation volume of about 25 ml/bag, and units banked more recently “may be linked to optimal banking practices.”

The guidelines recommend a minimum of eight high-resolution HLA typing for cord blood units and patients. A 4/6 match (HLA-A, -B, -DRB1) is acceptable, as is a 4/8 match (HLA-A, -B, -C, and -DRB1) or greater. In the case of a double-unit transplant, there is no need to match the units to each other.

“DSA must be considered on a case-by-case basis,” according to the guidelines. The patient’s diagnosis, prior immunosuppressive therapy, planned conditioning regimen, and DSA number/titer/specificity/complement fixation should be taken into consideration. DSA-targeted units should be avoided in patients with nonmalignant conditions and used with caution in patients with hematologic malignancies.

For single–cord blood units, the total nucleated cell dose should be at least 2.5 x 10⁷/kg, and the number of CD34+ cells should be at least 1.5 x 10⁵/kg. For double-unit transplants, the total nucleated cell dose should be at least 1.5 x 10⁷/kg for each unit, and the number of CD34+ cells should be at least 1.0 x 10⁵/kg for each unit.

The guidelines note that additional research is needed to inform how to balance cell dose against HLA match. However, cell dose should often take priority over HLA match for adults and larger pediatric patients, and HLA match can take priority in children, smaller adults, or patients with common HLA typing who have multiple units with a high cell dose.

The guidelines’ authors reported relationships with MolMed, NexImmune, AbbVie, Bellicum, Incyte, Medigene, Merck, Nektar, Novartis, Servier, Miltenyi, and the U.S. government/military.

[email protected]

SOURCE: Dehn J et al. Blood. 2019 Jul 10. doi: 10.1182/blood.2019001212.